Alzheimer's disease is a progressive disease resulting in senile dementia. Broadly speaking, the disease falls into two categories: late onset, which occurs in old age (65+ years) and early onset, which develops well before the senile period, i.e., between 35 and 60 years. In both types of the disease, the abnormalities tend to be more severe and widespread in cases beginning at an earlier age. Alzheimer's disease is characterized by at least two types of lesions in the brain, senile plaques and neurofibrillary tangles. Senile plaques are areas of disorganized neuropil up to 150 μm across with extracellular amyloid deposits at the center visible by microscopic analysis of sections of brain tissue. Neurofibrillary tangles are intracellular deposits of microtubule associated with tau protein consisting of two filaments twisted about each other in pairs.
The principal constituent of the plaques is a peptide termed amyloid beta (Aβ) or β-amyloid peptide. Aβ peptide is an internal fragment of 39-43 amino acids of a precursor protein termed amyloid precursor protein (APP). Several mutations within the APP protein have been correlated with the presence of Alzheimer's disease. Such mutations are thought to cause Alzheimer's disease by increased or altered processing of APP to Aβ, particularly processing of APP to increased amounts of the long form of Aβ (i.e., Aβ1-42 and Aβ1-43). Mutations in other genes, such as the presenilin genes, PS1 and PS2, are thought indirectly to affect processing of APP to generate increased amounts of long form Aβ. These observations indicate that Aβ, and particularly its long form, is a causative element in Alzheimer's disease.
One approach to treatment of Alzheimer's disease is the use of orally administered drugs. A problem with orally administered Alzheimer's drugs or nonsteroidal anti-inflammatory drugs is unpleasant side effects including severe nausea and gastric ulcers which patients develop following chronic use. Further, with chronic oral therapy the therapeutic value diminishes over time requiring dose escalation. In addition, limited transport of Alzheimer's drugs or other nonsteroidal anti-inflammatory drugs across the blood brain barrier increases the potential for systemic adverse side-effects. In order to maintain the same therapeutic affect with disease progression, the dose of Alzheimer's drugs taken orally must increase. In patients having adverse side-effects, treatment escalation is not possible. Thus, oral administration of Alzheimer's drugs is inherently dose-limiting. In addition to the problems just mentioned with orally administered Alzheimer's drugs or similar nonsteroidal anti-inflammatory drugs, the amount of drug entering the patient's blood system is minimized by uptake of the drugs by the gastrointestinal system.
Therefore, a need exists for improvements over the prior art, and more particularly for improved methods and systems for treating Alzheimer's disease.